The long-term goal of the applicants is to define the locus and mode of action of the thyroid hormones. Convincing evidence has been obtained that the mitochondrion may be a primary, and perhaps the primary, locus of action of thyroxine. Thyroxine has been shown to stimulate both mitochondrial protein synthesis as well as oxygen consumption in various tissues within minutes in vitro and within 3 hours in vivo. The aim of the current project is to define the underlying mechanism for this effect of thyroxine on mitochondria, to identify the protein, the synthesis of which is stimulated, and to clarify the relationship of this effect on mitochondria to the demonstrated stimulation of ribosomal protein synthesis and RNA polymerase activity.